| RRC ID |
87877
|
| Author |
Wang Y, Wang Y, Ding L, Ren X, Wang B, Wang L, Zhao S, Yue X, Wu Z, Li C, Liang X, Ma C, Gao L.
|
| Title |
Tim-4 reprograms cholesterol metabolism to suppress antiviral innate immunity by disturbing the Insig1-SCAP interaction in macrophages.
|
| Journal |
Cell Rep
|
| Abstract |
Accumulating evidence indicates that macrophages reshape their cholesterol metabolism in response to pathogens to support host defense. Intervention of host cholesterol homeostasis has emerged as a promising strategy for antiviral therapy. T cell immunoglobulin and mucin domain-containing molecule 4 (Tim-4) is indispensable in maintaining the homeostasis of macrophages. However, its role in antiviral innate immunity and cholesterol metabolism remains unknown. Here, we report that Tim-4 deficiency results in boosted interferon (IFN) signaling and decreased viral load. Mechanistically, Tim-4 disturbs the Insig1-SCAP interaction and promotes SCAP-SREBP2 complex translocation to the Golgi apparatus, eventually leading to the upregulation of cholesterol biosynthesis in macrophages, which limits the type I IFN response. Our findings demonstrate that Tim-4 suppresses type I IFN signaling by enhancing SREBP2 activation, delineating the role of Tim-4 in antiviral innate immunity and cholesterol metabolism, which sheds light on the mechanism by which Tim-4 orchestrates macrophage homeostasis.
|
| Volume |
41(9)
|
| Pages |
111738
|
| Published |
2022-11-29
|
| DOI |
10.1016/j.celrep.2022.111738
|
| PII |
S2211-1247(22)01616-3
|
| PMID |
36450259
|
| MeSH |
Cholesterol
Immunity, Innate*
Lipid Metabolism
Macrophages
|
| Resource |
| Human and Animal Cells |
THP-1 |
